Hexachlorocyclopentadiene
| |||
Names | |||
---|---|---|---|
IUPAC name
1,2,3,4,5,5-hexachlorocyclopenta-1,3-diene
| |||
Other names
graphlox, perchlorocyclopentadiene
| |||
Identifiers | |||
3D model (
JSmol ) |
|||
ChemSpider | |||
ECHA InfoCard
|
100.000.937 | ||
PubChem CID
|
|||
UNII | |||
CompTox Dashboard (EPA)
|
|||
| |||
| |||
Properties | |||
C5Cl6 | |||
Molar mass | 272.76 g·mol−1 | ||
Appearance | Pale-yellow to amber-colored liquid | ||
Odor | Pungent, unpleasant[1] | ||
Density | 1.702 g/cm3 | ||
Melting point | −10 °C (14 °F; 263 K) | ||
Boiling point | 239 °C (462 °F; 512 K) | ||
0.0002% (Reacts, 25°C)[1] | |||
Vapor pressure | 0.08 mmHg | ||
Hazards | |||
Occupational safety and health (OHS/OSH): | |||
Main hazards
|
Teratogen | ||
Flash point | 100 °C (212 °F; 373 K) | ||
NIOSH (US health exposure limits): | |||
PEL (Permissible)
|
none[1] | ||
REL (Recommended)
|
TWA 0.01 ppm (0.1 mg/m3)[1] | ||
IDLH (Immediate danger) |
N.D.[1] | ||
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
|
Hexachlorocyclopentadiene (HCCPD), also known as C-56, Graphlox, and HRS 1655, is an
Synthesis and production
Hexachlorocyclopentadiene is prepared by
- C5H6 + 6 Cl2 → C5H2Cl8 + 4 HCl
- C5H2Cl8 → C5Cl6 + 2 HCl
Besides manufacturers that produce the chemical for scientific synthesis and reference, there are two companies that produce HCCPD for industrial use: Velsicol Chemical LLC in the United States and Jiangsu Anpon Electrochemicals Co. in China. The first produces the chemical on a large scale to be used for producing rubber adherents, flame retardants and pesticides. Velsicol knows the dangers of handling HCCPD and therefore requires its buyers to go through a strict review and educational program on the storage, use and disposal of the chemical. The company also provides safety data sheets and a handling guide on its website, and delivers the chemical to purchasers all over the world.[6] Of the Chinese company less is known. It is said to be a company specialized in chloro-alkali and agrochemicals and operating as a subsidiary of China National Agrochemical Corporation.[7]
In addition, Hexachlorocyclopentadiene readily undergoes the
- aldrin from norbornadiene (the related dieldrin is a metabolite of aldrin)
- chlordane from cyclopentadiene, followed by chlorination
- epoxidation
- heptachlor from cyclopentadiene, followed by monochlorination
- isobenzan from dihydrofuran followed by chlorination
- cis-butene-1,4-diol, followed by esterification with SOCl2
- dienochlor
Reactions
HCCP is electrophilic. It degrades in base. Alcoholysis affords ketals C5Cl4(OR)2.[8]
HCCP readily undergoes Diels-Alder reactions with alkenes. This reaction is used to produce pesticides such as Aldrin (named after the reaction) and Isodrin. Most of these pesticides are no longer commercially available and banned by the Stockholm convention on persistent organic pollutants due to their toxicity to humans and animals.[9]
Biodegradation
In surface water,
Toxicokinetics
HCCPD absorption in the body occurs mostly through the lungs, gastrointestinal tract and skin. Overall the levels of HCCPD in blood were lower when administered through food compared to when inhalation was used. This may indicate a poor absorption in the gastrointestinal tract due to binding to the gastrointestinal contents. When HCCPD is absorbed, it is distributed to the liver, kidney and lungs. The organ with the highest concentration differs when comparing rats and mice. The highest concentration in rats is found in the kidney versus in the liver of mice.[5]
Absorption
The relevant absorption studies are done using
For multiple oral exposures in rats,
Toxicodynamics
Complete
The exact pathway for the complete metabolism of HCCPD is not known. There are contradicting results from different studies regarding the composition of excreted material. The metabolites were found to be polar in one study and nonpolar in the other. In addition, some of the potential metabolites such as hexachloro-2-cyclopentanone, hexachloro-3-cyclopentanone, hexachloroindone, or octachloro-3a,4,7,7a-tetrahydro-4,7-methanoindene-1,8-dione were not yet identified by extraction of excreted material.[5]
As the compound readily undergoes Diels–Alder reactions synthetically, it is possible that the HCCPD could react directly with cellular alkenes in a cycloaddition reaction. This might then explain why HCCPD causes effects at the point of contact for all the possible routes of exposure, in addition to the tissue-binding properties.[5]
Excretion
There is a slight difference in ratios of the amount excreted in urine and the amount excreted in feces between rats and mice. Though generally, the highest portion of
Indications (biomarkers)
Effects
Humans exposed to HCCPD do not show adverse health effects exclusive to that chemical. A small percentage of wastewater treatment workers who were exposed to water containing HCCPD in 1977 reported irritation of skin and eyes, chest discomfort, headaches, nausea and fatigue. In the long term, they showed irregularities in their liver function using tests that monitor enzyme levels. However, these irregularities could be due to many other compounds and variations in health.[11] Other proposed parameters for characterizing effects in humans, like urinary porphyrin excretion, were also tested for their potential use as a biomarker, but none were deemed significant enough. Experiments performed on laboratory animals like rats and mice show that a yellow-brown pigment forms in the epithelium of the nose after long-term inhalation exposure, even at low doses, which is considered a useful biomarker for long-term exposure.[5]
Unusual susceptibility
When there is pre-existing damage to organs involved in uptake or metabolism such as lungs and the liver, people can be more susceptible to HCCPD exposure because of their already compromised organ function. Because respiratory exposure seems to be the most prevalent route of exposure, people suffering from asthma are probably more susceptible to adverse effects than the general population.[11] Another group that is particularly vulnerable to hazardous chemicals is children. In their development there are critical periods where distinct structures and functions can be more susceptible towards disruption, and the damage done might only become apparent in a later stage of life. Absorption may differ for children because of their incompletely developed organs and larger surface to body weight ratio. Fortunately, it is very unlikely that small children are immediately exposed to HCCPD because it is only found as an impurity in pesticides and is not used in homes.[5]
Effects on animals
No studies were done on the lethality of humans in relation to HCCPD. It was however tested on animals and is postulated to have effects on brain and adrenal glands. In the brain, HCCPD or a metabolite thereof can react with lipids. In order to see degenerative brain effects in for example rats, the animals are exposed to a high dose of HCCPD concentration by inhalation. When dealing with low exposure levels, HCCPD reactivity makes the chance of reactive species in the blood at high concentrations very low. However, at higher doses the probability of transporting reactive material across the blood-brain barrier is higher.[5]
Short-term inhalation of HCCPD is
Oral effects
Single doses of HCCPD were found to be moderately toxic to animals if ingested orally. However, as the compound was not entirely pure (93.3%) while performing studies, some of the toxic effects could be attributed to the impurities, especially at high doses.
Data of oral effects on other species that mice and rats are limited. Single high doses of HCCPD resulted in increased effort to breathe in rats and rabbits alike. The lung tissues of these animals were
Dermal effects
Increasing dermal doses showed a shorter survival time for the animals. Lung effects of rabbits were examined in dermal animal studies, showing
The form in which HCCPD appears in the environment, so in its pure form or in solution, showed a striking effect on the epidermis of rabbits, guinea pigs and monkeys. Damage to the skin could be seen, namely discolored and inflamed skin. When the animals did not die by these lesions, they healed over time by itself.[5]
Inhalation effects
HCCPD is highly toxic to animals when inhaling its vapours. No human studies regarding lethality were done, but there has been an incident involving a waste water treatment centre where humans were exposed, from which most relevant human information is taken.
Human inhalation effects
There is data for human exposure to HCCPD for numerous organ systems. Waste water treatment plant and water cleanup crew workers were exposed after industrial release of the compound into the environment. The initial concentration of the compound in air was unknown but was later determined to be ranging between 0.27 and 0.97
In addition, elevated levels of lactic dehydrogenase was found in 11 out of 41 workers from the wastewater treatment. These levels was not nearly as high for workers from the water cleanup crew, but the aspartate aminotransferase levels were elevated for 12 out of 97 of these workers. These enzymes might indicate damage to heart, as well as to the liver. No evidence of heart function impairment was found in both worker groups though. The elevated levels in patients diminished after a period of 3 weeks.[5]
Animal inhalation effects
For prolonged exposure, significant differences occur between lab animal species. Where all mice died in the first week in a 13-week study, being exposed to 2 ppm HCCPD for 5 days a week, 6 hours a day, rats however survived until the third week. For a very low exposure of 0.04 ppm, 3 out of 20 mice died and none of the rats died. Chronic exposure of HCCPD at very low concentrations produced a yellow-brown pigment in the lung, tracheal and nasal epithelium in rats and mice. The pigmentation did not disappear after the exposure stopped.
For acute high exposures (1 hour, 42 ppm) all animals died, after showing difficulty breathing and gasping for air. Their lung tissues showed hemorrhagic lesions, inflammation, edema and necrosis in the bronchi. However recovery of the animals that survived was apparent 2 weeks after the treatment.
Cardiac and gastrointestinal function seemed not be impaired after exposure of HCCPD in rats, mice and monkeys. Moderate hepatic tissue degeneration was observed for acute inhalation. The same tissue degeneration was observed for longer experiments with lower concentrations.[5]
History
HCCPD is a highly toxic[12] organochlorine compound that was first mentioned as a diene in certain Diels-Alder reactions in 1930. The HCCPD chemical family quickly attracted increased attention with the discovery of its insecticidal properties in 1955 and extensive commercialization. However, due to extensive use, the HCCPD family of insecticides (chlordane, aldrin, dieldrin, endrin, heptachlor) became less effective as a result of genetic mutations of the targeted insects. The number of insects resistant to cyclodienes and lindane approached 300 by 1989.[2]
Later, in 1957, another use of the compound was found, namely as a
Today, almost all HCCPD derivatives have been banned or are under consideration for banning, according to the deliberations of the Stockholm Convention on Persistent Organic Pollutants. However, given that HCCPD is a versatile raw material for the synthesis of a wide range of end products, as of October 2021 it is still available commercially.[14]
References
- ^ a b c d e NIOSH Pocket Guide to Chemical Hazards. "#0315". National Institute for Occupational Safety and Health (NIOSH).
- ^ ISBN 978-3527306732.
- ISBN 978-3527306732.)
{{cite encyclopedia}}
: CS1 maint: multiple names: authors list (link - ^ Production of hexachlorocyclopentadiene McBee; Baranauckas Industrial and Engineering Chemistry; 1949, 41; p806
- ^ a b c d e f g h i j k l m n o p q U.S. Department of Health and Human services (1999). "Toxicological Profile for Hexachlorocyclopentadiene (HCCPD)".
- ^ "Hexachlorocyclopentadiene | Velsicol Chemical, LLC". Hexachlorocyclopentadiene | Velsicol Chemical, LLC.
- ^ "Company Overview of Jiangsu Anpon Electrochemical Co., Ltd". Bloomberg.
- .
- ^ "Stockholm Convention - Home page". www.pops.int.
- ^ EPA. 1984. Health effects assessment for hexachlorocyclopentadiene. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Research and Development, Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office. EPA/540/1-86/001
- ^ a b c Kominsky JR, Wisseman CL, Morse DL. 1980. Hexachlorocyclopentadiene contamination of a municipal wastewater treatment plant. Am Ind Hyg Assoc J 415.52-556
- ^ "Hexachlorocyclopentadiene Safety Data Sheet, Version 5" (PDF). Velsicol Chemical Corporation. January 2019. Retrieved 2021-10-01.
- ^ 2: Seymour, R.B; Deanin, R.D; History of Polymeric Composites;1987; VSP;
- ^ "Hexachlorocyclopentadiene: Versatile Intermediate for Multiple End-Uses". Velsicol Chemical Corporation. October 2021. Retrieved 2021-10-01.